Biomedical Engineering Reference
In-Depth Information
In an
in vitro
culture system, Witze et al. found that Wnt5a plays a per-
missive role in promoting directional migration of melanoma cells toward a
gradient of the chemokine CXCL12 by inducing an asymmetrically distrib-
uted Frizzled-containing receptor-actin-myosin polarity (W-RAMP)
structure (
Witze et al., 2008
). It should be pointed out that the study and
observation are made at single-cell level
in vitro
and it is not clear whether
the phenomenon is truly related to PCP. In addition, regulation of PCP
requires close cell-cell contact in a field of cells. In the zebrafish model,
injecting
wnt11
mRNA into one-cell stage embryos can rescue
slb
mutant
phenotype, suggesting its role in regulating CE is permissive (
Heisenberg
et al., 2000
). However, notably, the mutant embryos were not fully rescued
(57%
wnt11
-injected
slb
exhibited other abnormal phenotype) (
Heisenberg
et al., 2000
). Additionally,
ppt
mutant phenotype could not be rescued by
misexpressing
Wnt5b
. Instead, wnt5b-injected
ppt
embryos exhibited vari-
able malformations (
Kilian et al., 2003
). All these suggest that the instructive
role of Wnt5b or Wnt11 cannot be ruled out and maybe a better assay system
and/or readout is needed in addressing this issue. Indeed, more and more
evidence in different organisms indicates that Wnt gradients do provide di-
rectional information to regulate polarized cell behaviors in a group of cells.
A study in
Caenorhabditis elegans
found that the ground polarity is established
by instructive Wnt/EGL-20 activity via CAM-1 (a Ror receptor tyrosine
kinase) and Van Gogh/VANG-1 (
Green, Inoue, & Sternberg, 2008
). In
zebrafish, it has been shown that Wnt5b regulates gastrulation movements
by acting as an instructive cue through Ryk (
Lin et al., 2010
). In the mouse
developing palate, an essential role of Wnt5a in regulating directional cell
migration through Ror2 was demonstrated (
He et al., 2008
). Recently, it
is shown that Wnt5a controls directional outgrowth and A-P guidance of
commissural axons through core PCP proteins (
Shafer et al., 2011
).
Wnt11 has also been shown to act as an instructive cue. In the chick em-
bryo, Wnt11 signaling in early muscle fibers regulates their directional elon-
gation and orientation through the PCP pathway (
Fig. 11.1C
)(
Gros et al.,
2009
). The neural tube is necessary and sufficient to polarize muscle fibers,
and the myocytes are aligned in parallel to each other and along with the
A-P axis of the embryo.
Wnt11
expression at the medial border of somites
is induced by secreted Wnt1 and/or Wnt3a from the dorsal neural tube and
is required to control the polarized elongation of myocytes through the PCP
components. When the elongating myocytes are exposed to a localized ex-
ogenous source of Wnt11, myocyte elongation was redirected to be around
the localized exogenous Wnt11. When
Wnt11
is expressed in myocytes
